We have prepared compounds which inhibit the aromatase enzyme (estrogen synthetase) in vitro and have found some to have antifertility activity in the rat. Preliminary data with inhibitor treatment of rats bearing dimethylbenzanthracene (DMBA)-induced, estrogen -dependent, mammary cancer, shows that 80% of tumors regressed significantly in 4 weeks, 52% of which completely regressed. We propose to test other aromatase inhibitors and to prepare new ones for testing as antitumor agents in DMBA-treated rats. To establish aromatase inhibitors as a class of compounds with a property useful in breast cancer therapy, evidence for aromatase inhibition operating in vivo will be sought. Using the compound proved most effective, we will determine, 1) if the tumor regression caused by inhibitors can be overcome by administering estradiol during inhibitor treatment; 2) if blood estrogen levels in vivo are lowered by inhibitors and 3) if inhibitors have effects on other hormones including LH, testosterone and prolactin. Estrogen receptor levels will be measured in tumor tissue. Tumors lacking estrogen receptors are presumably hormone independent and would not be expected to respond to aromatase inhibitor treatment. Aromatase inhibitors will be also evaluated for other aspects of tumor growth, including estrogen receptors and prolactin.